Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

RBM5 (RNA binding motif protein 5)

Written2007-02Mirna Mourtada-Maarabouni
School of Life Sciences, Keele University, Keele, Staffs, ST5 5BG, United Kingdom

(Note : for Links provided by Atlas : click)


Alias (NCBI)LUCA-15
HGNC (Hugo) RBM5
HGNC Alias symbLUCA15
LocusID (NCBI) 10181
Atlas_Id 42069
Location 3p21.31  [Link to chromosome band 3p21]
Location_base_pair Starts at 50088919 and ends at 50119021 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping RBM5.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
DAPK1 (9q21.33)::RBM5 (3p21.31)HACL1 (3p25.1)::RBM5 (3p21.31)NFIX (19p13.2)::RBM5 (3p21.31)
RBM5 (3p21.31)::EPHA6 (3q11.2)
Note 3p21.3 is a putative human lung cancer tumor suppressor region. RBM5/LUCA-15 is a putative tumor suppressor gene


  RBM5/LUCA-15 splice variants. Boxes represent the exons, intronic sequences are represented by horizontal lines. The arrows point to the STOP codon in the protein coding sequence.
Description The gene spans about 30.03 Kb. Orientation plus strand. At least 25 exons.
Transcription Full length RBM5 has 3.1 Kb, 2448 bp open reading frame. The gene encodes a number of alternative splice variants, identified by reverse transcription polymerase chain reaction. One splice variant lacks exon 6, RBM5delta6. Three other RNA splice variants retain intronic sequences, RBM5+5+6 retains introns 5 and 6, RBM5+6 retains intron 6 and clone 26 which is a partial cDNA containing an open reading frame and terminates within intron 6. A 326 bp antisense cDNA that maps to the intronic region of RBM5, je2, has also been identified. Both, RBM5delta6 and clone 26 cDNAs have been cloned.


Description Full length RBM5 encodes a protein with a molecular mass of about 90 kDa (815 amino acids). The protein has two RNA Binding Domains (RBD), also recognized as RNA Recognition Motif (RRM). RBM5 structure also features other functional motifs, which includes two putative zinc-finger DNA binding motifs, two bipartite nuclear localisation signals and a G-patch domain (a conserved domain in eukaryotic RNA-processing proteins and type D retroviral polyproteins), suggesting a role for RBM5/LUCA-15 in RNA processing. In addition, the C-terminal region of RBM5/LUCA-15 contains several domains including a glutamine rich domain (362-385), which is thought to serve as protein-protein interaction site in certain RNA- and DNA- binding proteins.
RBM5delta6 encodes a protein of 17 kDa, due to a frameshift mutation caused by the deletion of exon 6. The only functional motif retained by this truncated protein is the arginine/glycine-rich amino terminal region. A putative 21 kDa is reported to be encoded by RBM5+5+6 and clone 26, as revealed by an in vitro transcription/translation study in rabbit reticulocyte lysate.
Expression Full length RBM5 and its alternative splice variants RNA are widely expressed in both primary tissue and cell lines. Northern blot analysis revealed higher expression in skeletal and heart muscles and pancreas. The expression of the full length RBM5 mRNA is reported to be high in adult thymus and low in the foetal thymus, suggesting that its expression is developmentally regulated. Full length RBM5/LUCA-15 is reported to be down-regulated in breast cancer specimens, in 82% of primary non-small-cell lung carcinoma specimens and in many lung cancer cell lines and in vestibular schwannomas (27 fold reduction). The expression of RBM5delta6 RNA is highest in transformed cells. The full length RBM5 protein is ubiquitously expressed in human tissues. It was found to be downregulated in 73% of primary non-small-cell lung carcinoma specimens compared to normal adjacent tissue. RBM5/LUCA-15 was one of the antigens identified by autologous antibody in patients with renal carcinoma. Overexpression of je2, the 326 bp antisense sequence, resulted in the downregulation of the RBM5 protein (95 kDa) and the upregulation of the 17 kDa protein (RBM5delta6).
Localisation RBM5 protein includes bipartite nuclear localisation signals suggesting its localisation to the nucleus.
Function RBM5/LUCA-15 is among the 35 genes located within the 370 kb overlapping lung cancer homozygous deletion region at 3p21.3. RBM5 has been implicated in the control of cell death by apoptosis and cell proliferation. RBM5's involvement in apoptosis and malignancy has been the focus of many recent studies, with all results converging on a role for RBM5/LUCA-15 as a Tumor Suppressor Gene (TSG). RBM5 splice variants have been shown to function as regulators of apoptosis. Stable expression of Je2, in human T-cell lines CEM-C7 and Jurkat produced marked inhibition of Fas-mediated apoptosis and conferred protection from apoptosis induced by other stimuli. RBM5delta6 inhibits CD95-mediated apoptosis as well as accelerating cell proliferation.
Overexpression of the full length RBM5 in CEM-C7 and Jurkat T-cell lines suppressed cell proliferation both by inducing apoptosis and by inducing cell cycle arrest in G1. Consistently, RBM5/LUCA-15 overexpression also inhibited human lung cancer cell growth (A549 non-small cell lung cancer line) by increasing apoptosis and inducing cell cycle arrest in G1. This inhibition of cell growth was reported to be associated with decreased cyclin A and phosphorylated RB and an increase in the level of the proapototic protein Bax. Introducing RBM5/LUCA-15 into breast cancer cells that had 3p21-22 deletions reduced both anchorage-dependent and anchorage-independent growth. RBM5/LUCA-15 also is reported to suppress anchorage-dependent and anchorage-independent growth in A9 mouse fibrosarcoma cells and to inhibit their tumour forming activity in nude mice. RBM5/LUCA-15 was one of the nine genes down-regulated in metastasis and it has been included in the 17 common gene signature associated with metastasis identified in multiple solid tumour types. Solid tumours carrying this gene expression signature had high rates of metastasis and poor clinical outcome. Microarray-based analysis of changes in gene expression caused by the modulation of the level of RBM5/LUCA-15 were carried out. Among 5603 genes on cDNA microarray, 35 genes, well known for their roles in the cell cycle as well as in apoptosis, were found to be differentially expressed as a result of RBM5/LUCA-15 overexpression in CEM-C7 cells.
These RBM5/LUCA-15 modulated genes include a number of cyclin-dependent kinase complexes, most notably CDK2 and three putative oncogenes which are down-regulated by RBM5/LUCA-15. These are Pim-1, a serine/threonine kinase, ITPA (inosine triphosphate pyrophosphatase) and Amplified in Breast cancer 1 (AIB1). Other functionally important genes modulated by RBM5/LUCA-15 are well established to play specific anti apoptotic roles such as BIRC4 (AIP3), BIRC3 (cIAP2, MIHC), Mcl-1, a member of the Bcl-2 family of apoptosis suppressors, and TRAF1, supporting a role for RBM5/LUCA-15 in apoptosis. Other genes upregulated by RBM5/LUCA-15 include Stat5b, Annexin I and Bone Morphogenetic Protein 5 (BMP5), implicated in apoptosis, immunosuppression and organ development respectively.
Homology RBM5 shares 30% amino acid sequence homology with its immediate telomeric neighbor, the putative tumor suppressor gene RBM6. Another RNA Binding Motif protein that shares high homology with RBM5 (53% at the amino acid level) is RBM10. The RBM10 gene is located on the X chromosome at p11.23. No function has yet been determined for RBM10. The mouse RBM5 gene is 90% identical on cDNA level and 97% on protein level. The fly proteome contain three similar proteins, of which CG4887 gene product shows 43% similarity. The rat binding protein S1-1 has similar domain structure and is close in amino acid sequence to RBM5.


Note Mutations in the RMB5 gene have not been found in lung cancer. RBM5 is reported to be downregulated in RAS-transformed Rat-1 cells, in samples from breast cancer, in human schwannomas and in about 75% of primary lung cancers specimens. RBM5 was one of the nine genes down-regulated in metastasis in primary tumors and it has been included in the 17 common gene signature associated with metastasis identified in multiple solid tumour types. Solid tumours carrying this gene expression signature had high rates of metastasis and poor clinical outcomes.

Implicated in

Entity Lung cancer and many other cancers
Disease RBM5 is located at the human chromosomal locus 3p21.3, which is strongly associated with lung cancer and many other cancers, including head and neck, renal, breast and female genital tract. More than 90% of freshly microdissected primary lung cancers display loss of heterozygosity (LOH) of 3p21.3. RBM5 is implicated in apoptosis and in cell cycle regulation.
Oncogenesis The ability of RBM5/LUCA-15 to inhibit the growth of transformed cells fulfils one of the criteria for a tumor suppressor. The simultaneous changes in proliferation and inhibition of apoptosis brought about by dysregulation of the RBM5/LUCA-15 locus are likely to be of major significance in oncogenesis.


G-patch: a new conserved domain in eukaryotic RNA-processing proteins and type D retroviral polyproteins.
Aravind L, Koonin EV
Trends in biochemical sciences. 1999 ; 24 (9) : 342-344.
PMID 10470032
Conserved structures and diversity of functions of RNA-binding proteins.
Burd CG, Dreyfuss G
Science (New York, N.Y.). 1994 ; 265 (5172) : 615-621.
PMID 8036511
Molecular cloning of a candidate tumor suppressor gene, DLC1, from chromosome 3p21.3.
Daigo Y, Nishiwaki T, Kawasoe T, Tamari M, Tsuchiya E, Nakamura Y
Cancer research. 1999 ; 59 (8) : 1966-1972.
PMID 10213508
A homozygous deletion on chromosome 3 in a small cell lung cancer cell line correlates with a region of tumor suppressor activity.
Daly MC, Xiang RH, Buchhagen D, Hensel CH, Garcia DK, Killary AM, Minna JD, Naylor SL
Oncogene. 1993 ; 8 (7) : 1721-1729.
PMID 8390035
DEF-3(g16/NY-LU-12), an RNA binding protein from the 3p21.3 homozygous deletion region in SCLC.
Drabkin HA, West JD, Hotfilder M, Heng YM, Erickson P, Calvo R, Dalmau J, Gemmill RM, Sablitzky F
Oncogene. 1999 ; 18 (16) : 2589-2597.
PMID 10353602
LUCA15, a putative tumour suppressor gene encoding an RNA-binding nuclear protein, is down-regulated in ras-transformed Rat-1 cells.
Edamatsu H, Kaziro Y, Itoh H
Genes to cells : devoted to molecular & cellular mechanisms. 2000 ; 5 (10) : 849-858.
PMID 11029660
Human lung cancer antigens recognized by autologous antibodies: definition of a novel cDNA derived from the tumor suppressor gene locus on chromosome 3p21.3.
Güre AO, Altorki NK, Stockert E, Scanlan MJ, Old LJ, Chen YT
Cancer research. 1998 ; 58 (5) : 1034-1041.
PMID 9500467
Differential elimination of 3p and retention of 3q segments in human/mouse microcell hybrids during tumor growth.
Imreh S, Kost-Alimova M, Kholodnyuk I, Yang Y, Szeles A, Kiss H, Liu Y, Foster K, Zabarovsky E, Stanbridge E, Klein G
Genes, chromosomes & cancer. 1997 ; 20 (3) : 224-233.
PMID 9365829
A group of NotI jumping and linking clones cover 2.5 Mb in the 3p21-p22 region suspected to contain a tumor suppressor gene.
Kashuba VI, Szeles A, Allikmets R, Nilsson AS, Bergerheim US, Modi W, Grafodatsky A, Dean M, Stanbridge EJ, Winberg G
Cancer genetics and cytogenetics. 1995 ; 81 (2) : 144-150.
PMID 7621411
Deletions of the short arm of chromosome 3 in solid tumors and the search for suppressor genes.
Kok K, Naylor SL, Buys CH
Advances in cancer research. 1997 ; 71 : 27-92.
PMID 9111863
The 630-kb lung cancer homozygous deletion region on human chromosome 3p21.3: identification and evaluation of the resident candidate tumor suppressor genes. The International Lung Cancer Chromosome 3p21.3 Tumor Suppressor Gene Consortium.
Lerman MI, Minna JD
Cancer research. 2000 ; 60 (21) : 6116-6133.
PMID 11085536
The antiapoptotic RBM5/LUCA-15/H37 gene and its role in apoptosis and human cancer: research update.
Maarabouni MM, Williams GT
TheScientificWorldJournal. 2006 ; 6 : 1705-1712.
PMID 17195868
Candidate tumor suppressor LUCA-15/RBM5/H37 modulates expression of apoptosis and cell cycle genes.
Mourtada-Maarabouni M, Keen J, Clark J, Cooper CS, Williams GT
Experimental cell research. 2006 ; 312 (10) : 1745-1752.
PMID 16546166
3p21.3 tumor suppressor gene H37/Luca15/RBM5 inhibits growth of human lung cancer cells through cell cycle arrest and apoptosis.
Oh JJ, Razfar A, Delgado I, Reed RA, Malkina A, Boctor B, Slamon DJ
Cancer research. 2006 ; 66 (7) : 3419-3427.
PMID 16585163
A candidate tumor suppressor gene, H37, from the human lung cancer tumor suppressor locus 3p21.3.
Oh JJ, West AR, Fishbein MC, Slamon DJ
Cancer research. 2002 ; 62 (11) : 3207-3213.
PMID 12036935
A molecular signature of metastasis in primary solid tumors.
Ramaswamy S, Ross KN, Lander ES, Golub TR
Nature genetics. 2003 ; 33 (1) : 49-54.
PMID 12469122
Antigens recognized by autologous antibody in patients with renal-cell carcinoma.
Scanlan MJ, Gordan JD, Williamson B, Stockert E, Bander NH, Jongeneel V, Gure AO, Jäger D, Jäger E, Knuth A, Chen YT, Old LJ
International journal of cancer. Journal international du cancer. 1999 ; 83 (4) : 456-464.
PMID 10508479
RNA binding motif (RBM) proteins: a novel family of apoptosis modulators?
Sutherland LC, Rintala-Maki ND, White RD, Morin CD
Journal of cellular biochemistry. 2005 ; 94 (1) : 5-24.
PMID 15514923
A comparison of genomic structures and expression patterns of two closely related flanking genes in a critical lung cancer region at 3p21.3.
Timmer T, Terpstra P, van den Berg A, Veldhuis PM, Ter Elst A, Voutsinas G, Hulsbeek MM, Draaijers TG, Looman MW, Kok K, Naylor SL, Buys CH
European journal of human genetics : EJHG. 1999 ; 7 (4) : 478-486.
PMID 10352938
Construction of a 600-kilobase cosmid clone contig and generation of a transcriptional map surrounding the lung cancer tumor suppressor gene (TSG) locus on human chromosome 3p21.3: progress toward the isolation of a lung cancer TSG.
Wei MH, Latif F, Bader S, Kashuba V, Chen JY, Duh FM, Sekido Y, Lee CC, Geil L, Kuzmin I, Zabarovsky E, Klein G, Zbar B, Minna JD, Lerman MI
Cancer research. 1996 ; 56 (7) : 1487-1492.
PMID 8603390
cDNA microarray analysis of vestibular schwannomas.
Welling DB, Lasak JM, Akhmametyeva E, Ghaheri B, Chang LS
Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology. 2002 ; 23 (5) : 736-748.
PMID 12218628


This paper should be referenced as such :
Mourtada-Maarabouni, M
RBM5 (RNA binding motif protein 5)
Atlas Genet Cytogenet Oncol Haematol. 2007;11(3):213-216.
Free journal version : [ pdf ]   [ DOI ]

External links

HGNC (Hugo)RBM5   9902
Entrez_Gene (NCBI)RBM5    RNA binding motif protein 5
AliasesG15; H37; LUCA-15; LUCA15; 
GeneCards (Weizmann)RBM5
Ensembl hg19 (Hinxton)ENSG00000003756 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000003756 [Gene_View]  ENSG00000003756 [Sequence]  chr3:50088919-50119021 [Contig_View]  RBM5 [Vega]
ICGC DataPortalENSG00000003756
TCGA cBioPortalRBM5
AceView (NCBI)RBM5
Genatlas (Paris)RBM5
SOURCE (Princeton)RBM5
Genetics Home Reference (NIH)RBM5
Genomic and cartography
GoldenPath hg38 (UCSC)RBM5  -     chr3:50088919-50119021 +  3p21.31   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)RBM5  -     3p21.31   [Description]    (hg19-Feb_2009)
GoldenPathRBM5 - 3p21.31 [CytoView hg19]  RBM5 - 3p21.31 [CytoView hg38]
Genome Data Viewer NCBIRBM5 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AB208813 AB586690 AF091263 AF103802 AF107493
RefSeq transcript (Entrez)NM_005778
Consensus coding sequences : CCDS (NCBI)RBM5
Gene ExpressionRBM5 [ NCBI-GEO ]   RBM5 [ EBI - ARRAY_EXPRESS ]   RBM5 [ SEEK ]   RBM5 [ MEM ]
Gene Expression Viewer (FireBrowse)RBM5 [ Firebrowse - Broad ]
GenevisibleExpression of RBM5 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)10181
GTEX Portal (Tissue expression)RBM5
Human Protein AtlasENSG00000003756-RBM5 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Conserved Domain (NCBI)RBM5
Human Protein Atlas [tissue]ENSG00000003756-RBM5 [tissue]
Protein Interaction databases
Ontologies - Pathways
PubMed98 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Fri Oct 8 21:26:46 CEST 2021

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us